2.Food-derived bioactive peptides: health benefits, structure‒activity relationships, and translational prospects.
Hongda CHEN ; Jiabei SUN ; Haolie FANG ; Yuanyuan LIN ; Han WU ; Dongqiang LIN ; Zhijian YANG ; Quan ZHOU ; Bingxiang ZHAO ; Tianhua ZHOU ; Jianping WU ; Shanshan LI ; Xiangrui LIU
Journal of Zhejiang University. Science. B 2025;26(11):1037-1058
Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans
;
Peptides/therapeutic use*
;
Structure-Activity Relationship
;
Functional Food
;
Diabetes Mellitus, Type 2/drug therapy*
;
Biological Availability
;
Alzheimer Disease/drug therapy*
;
Inflammatory Bowel Diseases/drug therapy*
;
Hypertension/drug therapy*
;
Liver Diseases/drug therapy*
;
Bioactive Peptides, Dietary
3.Emerging evidence of inter-organ interaction on drug transporters under liver injury.
Ling JIANG ; Ying DENG ; Ruijing MU ; Wenke FENG ; Xiaonan LIU ; Li LIU
Chinese Journal of Natural Medicines (English Ed.) 2025;23(6):687-699
Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
Humans
;
Liver/drug effects*
;
Animals
;
Chemical and Drug Induced Liver Injury/metabolism*
;
Membrane Transport Proteins/metabolism*
;
Biological Transport
;
Liver Diseases/drug therapy*
;
Pharmaceutical Preparations/metabolism*
4.First-in-class drug oroxylin A tablets for treating hepatic and gastrointestinal disorders: from preclinical development to clinical research.
Chengju LUO ; Xuhong LI ; Yuan GAO ; Junyi YANG ; Weiming FANG ; Libin WEI
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):801-814
Oroxylin A (OA) is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis. Currently, OA is obtainable through chemical synthesis and exhibits polypharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, and multi-organ protective effects. The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma (HCC) treatment. Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal (GI) disorders, including HCC, hepatic fibrosis, fatty liver disease, hepatitis, liver injury, colitis, and colorectal cancer (CRC). OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways, including those associated with apoptosis, oxidative stress, inflammation, glucolipid metabolism, and fibrosis activation. The oral pharmacokinetics of OA is characterized by phase II metabolism, hydrolysis, and enterohepatic recycling. This review provides a comprehensive overview of the critical stages involved in the development of OA tablets, presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases. It encompasses the synthesis of active pharmaceutical ingredients, pharmacokinetics, pharmacological efficacy, toxicology, drug delivery, and recent advancements in clinical trials. Importantly, this review examines the potential mechanisms by which OA may influence the gut-liver axis, hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.
Humans
;
Flavonoids/pharmacokinetics*
;
Tablets
;
Animals
;
Gastrointestinal Diseases/drug therapy*
;
Liver Diseases/drug therapy*
;
Drug Development
;
Clinical Trials as Topic
;
Scutellaria baicalensis/chemistry*
5.Discovery of bioactive polycyclic polyprenylated acylphloroglucinol from Hypericum patulum that protects against hepatic ischemia/reperfusion injury.
Bo TAO ; Xiangli ZHAO ; Zhengyi SHI ; Jie LI ; Yulin DUAN ; Xiaosheng TAN ; Gang CHEN ; Changxing QI ; Yonghui ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(9):1104-1110
Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control*
;
Animals
;
Hypericum/chemistry*
;
Phloroglucinol/administration & dosage*
;
Mice
;
Humans
;
Male
;
Liver/blood supply*
;
Apoptosis/drug effects*
;
Molecular Structure
;
Protective Agents/pharmacology*
;
Hepatocytes/drug effects*
;
Mice, Inbred C57BL
;
Liver Diseases/drug therapy*
6.Polysaccharides from Chinese herbal medicine: a review on the hepatoprotective and molecular mechanism.
Jifeng LI ; Haolin GUO ; Ying DONG ; Shuo YUAN ; Xiaotong WEI ; Yuxin ZHANG ; Lu DONG ; Fei WANG ; Ting BAI ; Yong YANG
Chinese Journal of Natural Medicines (English Ed.) 2024;22(1):4-14
Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.
Humans
;
Drugs, Chinese Herbal/pharmacology*
;
Liver Diseases/drug therapy*
;
Antioxidants
;
Polysaccharides/therapeutic use*
;
Medicine, Chinese Traditional
7.Electroacupuncture at acupoints of liver meridian for diminished ovarian reserve of liver depression: a randomized controlled trial.
Qiuping LUO ; Zhihong YANG ; Lingmin JIN ; Panbi CHEN ; Yun JIANG ; Qingke LI ; Wei ZHANG ; Xiaofang YANG
Chinese Acupuncture & Moxibustion 2024;44(11):1261-1266
OBJECTIVE:
To observe the therapeutic effect of electroacupuncture at acupoints of liver meridian in patients with diminished ovarian reserve (DOR) of liver depression.
METHODS:
A total of 62 patients with DOR of liver depression were randomly divided into an electroacupuncture group (31 cases, 1 case discontinued) and a western medication group (31 cases, 1 case was eliminated). Electroacupuncture was applied at bilateral Taichong (LR 3), Ligou (LR 5), Ququan (LR 8), Jimai (LR 12) in the electroacupuncture group, with continuous wave, in frequency of 2 Hz and current of 0.5-1.0 mA, 30 min each time, once every other day, 3 times a week. Femoston was taken orally in the western medication group, oral estradiol tablets were taken for the first 14 days, followed by oral estradiol/progesterone complex tablets for the rest 14 days, 1 tablet a day. Both groups were treated for 3 consecutive menstrual cycles. Before and after treatment, the scores of TCM syndrome, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed, serum levels of follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were detected, and antral follicle count (AFC), peak systolic velocity (PSV) and resistance index (RI) of ovarian artery were measured by color Doppler ultrasound in the two groups, and the clinical efficacy was evaluated after treatment.
RESULTS:
After treatment, the scores of primary symptom and secondary symptom, as well as the total scores of TCM syndrome were decreased compared with those before treatment (P<0.01), the scores of SAS and SDS, as well as the serum FSH levels and RI of ovarian artery were decreased compared with those before treatment (P<0.01), while the serum AMH levels, AFC and PSV of ovarian artery were increased compared with those before treatment (P<0.05, P<0.01) in the two groups. After treatment, in the electroacupuncture group, the primary symptom score of TCM syndrome was higher than that in the western medication group (P<0.01), the secondary symptom score of TCM syndrome and the scores of SAS and SDS were lower than those in the western medication group (P<0.05, P<0.01). The total effective rate was 70.0% (21/30) in the electroacupuncture group and 73.3% (22/30) in the western medication group respectively, there was no significant difference in the total effective rate between the two groups (P>0.05).
CONCLUSION
Electroacupuncture at acupoints of liver meridian can effectively improve the clinical symptoms, anxiety and depression, regulate the serum sex hormone levels, increase AFC and improve ovarian blood supply in DOR patients of liver depression.
Humans
;
Female
;
Electroacupuncture
;
Adult
;
Acupuncture Points
;
Meridians
;
Ovarian Reserve
;
Young Adult
;
Liver Diseases/physiopathology*
;
Liver/metabolism*
;
Ovary/physiopathology*
;
Treatment Outcome
;
Depression/therapy*
8.Application of peer-assisted learning based on Mini-CEX combined with DOPS evaluation in the teaching of autoimmune liver diseases.
Yansheng LIU ; Jiangyi ZHU ; Yulong SHANG ; Ying HAN
Chinese Journal of Cellular and Molecular Immunology 2024;40(12):1146-1150
Objective To explore the effects of peer assistance model based on mini-clinical evaluation exercise (Mini-CEX) combined with direct observation of procedural skill (DOPS) in the teaching of autoimmune liver diseases (AILDs). Methods A total of 115 residents receiving training in the Department of Gastroenterology of Xijing Hospital were selected and divided into a control group and an experimental group according to the order in which they came to the department. The control group received traditional teaching mode, while the experimental group underwent peer assistance model based on Mini-CEX combined with DOPS. Results The experimental group showed significantly higher scores in both clinical competence and medical record documentation compared to the control group. In addition, the experimental group reported higher satisfaction levels in terms of self-learning ability, learning interest, communication skills and cooperation ability. The overall satisfaction of the experimental group is higher than that of the control group. Conclusion The use of peer assisted learning mode based on Mini-CEX and DOPS in the AILD teaching could improve the teaching effects.
Humans
;
Autoimmune Diseases/therapy*
;
Liver Diseases/therapy*
;
Male
;
Female
;
Peer Group
;
Clinical Competence
;
Adult
;
Teaching
;
Learning
9.Research progress in pharmacological effectsand mechanism of Fel Ursi against cardiovascular and cerebrovascular diseases.
Li-Dan ZHU ; Jie LIAO ; Xiao-Yan LU ; Xiao-Hui FAN
China Journal of Chinese Materia Medica 2023;48(23):6307-6314
Fel Ursi is a dried product obtained from the gallbladder of Ursidae animals, such as Selenarctos thibetanus or Ursus arctos, through gallbladder surgery for bile drainage. It is one of the rare animal medicinal materials in China and is known for its therapeutic effects, including clearing heat, removing toxins, extinguishing wind, relieving spasms, clearing the liver, and improving vision. Research has also found that Fel Ursi has pharmacological effects against cardiovascular and cerebrovascular diseases, such as anti-inflammatory, anti-apoptotic, and antioxidant stress properties. Recently, numerous studies have confirmed the close relationship between cardiovascular and cerebrovascular diseases and the gut microbiota as well as gut metabolites. Fel Ursi contains bile acid components that may have bidirectional regulatory effects on the gut microbiota and gut metabolites. This aspect could represent a potential therapeutic pathway for Fel Ursi in the treatment of cardiovascular and cerebrovascular diseases. This article comprehensively summarized relevant literature in China and abroad, reviewed the research progress on the pharmacological effects of Fel Ursi against cardiovascular and cerebrovascular diseases, and explored the impact of Fel Ursi on gut microbiota and gut metabolites, thereby aiming to provide references for further in-depth research and clinical application of Fel Ursi.
Animals
;
Cerebrovascular Disorders/drug therapy*
;
Bile Acids and Salts
;
Lung
;
Liver
;
Ursidae
;
Cardiovascular Diseases/drug therapy*
10.Therapeutic potential and mechanism of Chinese herbal medicines in treating fibrotic liver disease.
Yanwei LI ; Yunrui LU ; Mozuo NIAN ; Qiuju SHENG ; Chong ZHANG ; Chao HAN ; Xiaoguang DOU ; Yang DING
Chinese Journal of Natural Medicines (English Ed.) 2023;21(9):643-657
Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness.
Humans
;
Drugs, Chinese Herbal/therapeutic use*
;
Fibrosis
;
Liver Diseases/drug therapy*
;
Treatment Outcome
;
Liver Cirrhosis/drug therapy*

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